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Effect of rosiglitazone and 15-deoxy-Δ 12,14 -prostaglandin J 2 on bleomycin-induced lung injury

2005; European Respiratory Society; Volume: 25; Issue: 2 Linguagem: Inglês

10.1183/09031936.05.00049704

1399-3003

Tiziana Genovese, Salvatore Cuzzocrea, Rosanna Di Paola, Emanuela Mazzon, Claudio Mastruzzo, Paolo N. Catalano, Maria Angela Sortino, Nunzio Crimi, A. P. Caputi, Christoph Thiemermann, Carlo Vancheri,

Inflammatory mediators and NSAID effects

Thiazolidinedione rosiglitazone and 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), are two peroxisome proliferator-activated receptor (PPAR)-γ ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ 2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury. An increase in immunoreactivity to nitrotyrosine, poly(ADP ribose) polymerase (PARP) and inducible nitric oxide synthase as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated mice. Administration of the two PPAR-γ agonists rosiglitazone (10 mg·kg −1 i.p. ) and 15d-PGJ 2 (30 µg·kg −1 i.p. ) significantly reduced the: 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) oedema formation, and 5) histological evidence of lung injury. Administration of rosiglitazone and 15d-PGJ 2 also markedly reduced the nitrotyrosine, PARP and inducible nitric oxide synthase formation. In addition, treatment with the PPAR-γ antagonist bisphenol A diglycidyl ether (1 mg·kg −1 i.p. 30 min before the rosiglitazone or 15d-PGJ 2 ) significantly antagonised the effect of the two PPAR-γ agonists. These results demonstrate that the two peroxisome proliferator-activated receptor-γ agonists, rosiglitazone and 15-deoxy-Δ 12,14 -prostaglandin J 2 , significantly reduce lung injury induced by bleomycin in mice.